User:Eric Martz/Sandbox 0

Proposed Article Title: Knots in Proteins

A piece of string, or a protein chain, is deemed to contain a knot when pulling on the ends would leave a knot. When the ends of most folded protein chains are "pulled", they resolve to a straight chain between the pulled ends: no knot remains. In this article, only knots in the peptide-bonded amino acid chain are considered; knots resulting from disulfide bonds or hydrogen bonds are excluded. Knots in protein chains are rare, and the mechanisms by which they form and their functions remain subjects of experimentation and discussion. Four types of knots have been found in protein chains, examples of three of which (41, 52, 61) are discussed below.

Figure-of-eight knot in acetohydroxy acid isomeroreductase
William R. Taylor developed an algorithm for detecting knots in protein backbones, which he reported in 2000. He scanned 3,440 sequence-different published protein structures from the Protein Data Bank. Only eight genuine knots were found, most of which were simple trefoil knots (overhand knots) and had been previously described. However several knots were detected in proteins not previously recognized as knotted. One was in acetohydroxy acid isomeroreductase ("AAIR", 1yve, 1qmg), and was particularly interesting because of how deeply it sits in the folded protein backbone (far away from the ends) and because it is a more complicated figure-of-eight knot.

Taylor states "Pulling the ends of a given piece of string will usually decide whether it is knotted or not. Because we hold the ends, the string and our body form a closed circle and there is no danger of untying the knot as it is pulled." "The ends of protein chains (being charged) tend to lie on the surface ...." "An alternative approach is to invert the problem: rather than extending the termini outwards, these can be left fixed and the rest of the protein made to shrink around them. This was done [mathematically] by contracting the protein as if it were a rubber band."




 * Acetohydroxy acid isomeroreductase (restore initial scene ) from spinach (1yve) is the protein containing Taylor's figure-of-eight knot. Here is shown only one chain (I) of the biological unit, which is a homodimer.


 * Most of the chain is here translucent, except for the knot-containing segment 312-545.


 * Only the knot-containing segment 312-545 is shown here.


 * The ends of the knot-containing segment are fixed, while the intervening backbone mathematically shrinks revealing the knot (see Animation Methods).


 * For comparision, here chain "1" of triosephosphate isomerase (1tph), which has a similar length (247 residues) to the knotted region of 1yve (sequence range 312-545, length 234).
 * Mathematical shrinking, while fixing the positions of the ends, reveals that no knot is present.

Subsequent to Taylor's work, figure-of-eight knots were found in three other ketol acid reductoisomerases, as well as in several phytochromes, a transcriptional regulator, and a virus core protein (see list at the pKnot server). Also, more complex knots were found, described below.

Knot Servers
These protein knot servers offer rotatable 3D graphics showing simplified knots.

pKnot

 * Server: pKnot.
 * Generates a morph "movie" of shrinking (holding the ends fixed), which can be played in OpenAstexViewer, or downloaded as a multiple-model PDB file, e.g. for animation in Jmol.
 * Visualization: appears to be in OpenAstexViewer. In Safari (but not in Firefox) on OS X, moving away from the browser tab containing the viewer causes the view to disappear when you return, and any options you checked to be lost.
 * Lists all knots in the PDB categorized by knot type (click the small link Knot table near the upper left of the main page, in a black bar). List includes core sequence range, and depth (but the "depth" is a single value not defined on the server). "Length" in the list appears to be the length of the entire protein chain, not the length of the knotted portion.
 * Upload PDB file: YES, and you can specify a sequence range for analysis.

knots.mit.edu

 * Server: knots.mit.edu.
 * Visualization: Jmol showing the chain with the knotted region colored, and the simplified knot (no movie).
 * Lists knots (a shorter list than at the pKnot server). List includes core sequence range plus other numbers that are not labeled. "Length" in the list appears to be the length of the entire protein chain, not the length of the knotted portion.
 * Upload PDB file: YES.

Knot Categories
There are 176 pages mentioning "knot" in September, 2010, and 41 Categories that have been assigned automatically and suffer from many alternative phrases for the same thing. You can display the current list of "knots" categories using a search limited to the Category namespace: Searching for the singular "knot" also gave 41 Categories in Sept. 2010.
 * Search for "knots" Categories in Proteopedia

Entries not in a knot category
A few pages that mention "knot" are not assigned to a knot Category.
 * 1mxi Methyltransferase with a Cofactor Bound at a Site Formed by a Knot
 * 2c4b INHIBITOR CYSTINE KNOT
 * 1k3r Methyltransferase with a Knot

Methods
Please see Knots in Proteins - Methods.

Content Attribution
Animations and models used in this article for the figure-of-eight knot were developed in August, 2000 by User:Eric Martz at Knots in Proteins, where the animations utilized the now defunct MDL Chime plugin.

Data for the figure-of-eight and unknotted comparison morphs were kindly provided by William R. Taylor (Division of Mathematical Biology, National Institute for Medical Research, the Ridgeway, Mill Hill, London UK) in 2000.